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Thursday, September 18, 2014

Malaria control now may not foretell the future

There are hailstorms, landslides, droughts, malaria and...the State. These are inescapable evils: such there always have been and there always will be.
Carlo Levi, Christ Stopped at Eboli: The Story of a Year, 1945

Malaria was once endemic in southern Europe, the UK, and the Americas. It was in Greece at least 4000 years ago, and reached the Americas with or shortly after Columbus, eventually becoming an 'inescapable evil' when the slave trade was at its height. With mosquito control due to DDT, cleaning up of standing water and other measures, the disease was essentially eliminated in the US and Canada and some parts of South America by 1950. But the factors that maintain malaria in a population are complex, and it's possible that with climate change, global transfer of goods and increasing immigration from endemic areas, this, and other mosquito-borne diseases could return.

A recent episode of the BBC Radio 4 program, Costing the Earth, discussed the increasing spread of a number of mosquito species in the UK and throughout Europe. In particular, the Asian tiger mosquito(Aedes albopictus), a voracious biter, has been spreading north from the Mediterranean for several decades. It doesn't carry malaria, but it is a vector for other significant diseases including Yellow fever, Chikungunya, and nematodes that cause filariasis.

The Costing the Earth episode pointed out that the mosquito is spreading for multiple reasons, perhaps a perfect storm of causation: temperatures are warming, sustained drought in the UK has meant that more and more people are collecting rain in buckets, to use in watering their gardens, and these standing pots of water have turned out to be a great reservoir for mosquito breeding, there is sustained wetland restoration happening in the country, tires shipped into the UK are also frequently full of stagnant water and thus mosquitoes and a number of species are entering the country via this route. And so on. But, mosquitoes that carry and transmit malaria still live in areas where malaria is no longer endemic, including the UK and the US. So, it's not the absence of the vector that explains the absence of disease.

The dynamics of epidemics are well-understood, in mathematical, ecological and cultural detail (Aeon magazine has just published an excellent and accessible description of the mathematics of epidemics). In the case of malaria, generally speaking, to maintain the disease in a population the population must be over a given size, there must be a reservoir of infected individuals for the mosquitoes to feed on, there must be a large enough mosquito population to transmit the disease to enough susceptible individuals, the fatality rate can't be so high that the parasite is quickly eliminated by death, environmental conditions must be favorable to the vector, and so on. And, cultural factors must be favorable as well, so that, e.g., mosquitoes can find people to feed on or to infect at the right time of day or night. That is, there are multiple factors required to maintain disease in a population, and often the infection can be halted by interfering with any one of them.

So, eliminating the vector, mosquitoes that carry the malarial parasite, is one approach to eliminating malaria, and as anything that breaks the chain of infection, vector control can successfully control the disease. But, it's not required. Reducing the prevalence of the disease to a level at which the host/vector ratio is no longer sufficient to transmit the disease widely, as was done in the US and Europe in the 1940's, is another way. So, we in non-endemic areas of the world live with, and are bitten by potential vectors with no fear of infection with malaria, though now West Nile virus and Chikungunya are another story. Indeed, this map shows the distribution of vectors or potential vectors around the globe.

Global Distribution of Dominant or Potentially Important Malaria Vectors

From Kiszewksi et al., 2004. American Journal of Tropical Medicine and Hygiene 70(5):486-498, via the CDC.

Thus, where malaria has been eliminated, continued control depends on there being not enough infected individuals to sustain the infection. Of course, this could change. Southern Europe may be seeing the re-introduction of malaria, for example -- the disease has been spreading in Greece now for the first time in four decades. In this case it can be blamed on the economic crisis and austerity because the government has not been able to pay for mosquito spraying, but the spread of malaria can't be blamed on mosquitoes alone; they've got to have an increased number of infected people to feed on as well. And it's not just malaria -- other heretofore neglected, unexpected, tropical diseases are reaching the shores of the US, and Europe, Chikungunya being one example.

We live in a dynamic, changing, interconnected world. Malaria rates seem to have been declining in Africa and Asia, and research into better prevention and control is ongoing, and researchers can claim many successes. But, like the proverbial fluttering of the butterfly wing that unpredictably causes climatic chaos far away, if innocuous acts like saving rain water in the UK can have widespread and unpredicted effects like increasing the spread of previously unknown mosquitoes, and thus potentially disease, it's hard to reliably predict that malaria will remain controlled in currently non-endemic areas. This is not to be alarmist, but simply to point out that it's a bit hubristic to believe we can predict anything so complex, particularly when it requires predicting future environments. We've said the same many times before about predicting complex disease from genes.

Carlo Levi (1902 - 1975) was an Italian painter, writer and physician. Because of his political activism during the fascist era, he was exiled to a small southern town in Lucania, where he spent several years painting, writing and attending to the medical needs of the inhabitants there. He wrote about this time in his book, Christ Stopped at Eboli, published in 1945. It's a fascinating story; political, ethnographic, scientific (or quasi so). Malaria was a fact of life in southern Italy at the time, and Levi mentions it often in the book. Including in this passage:

In this region malaria is a scourge of truly alarming proportions; it spares no one and when it is not properly cared for it can last a lifetime. Productive capacity is lowered, the race is weakened, the savings of the poor are devoured; the result is a poverty so dismal and abject that it amounts to slavery without hope of emancipation. Malaria arises from the impoverishment of the deforested clayey land, from neglected water, and inefficient tilling of the soil; in its turn it generates in a vicious circle the poverty of the peasants. Public works on a large scale are necessary to uproot it. The four main rivers of Lucania ... besides a host of lesser streams, should be dammed up; trees should be planted on the mountainsides; good doctors, hospitals, visiting nurses, medicines, and preventive measures should be made available to all. Even improvements on a limited scale would have some effect... But a general apathy prevails and the peasants continue to sicken and die.

Levi may not have entirely understood the cause of malaria, but he clearly understood the vicious cycle of malaria and poverty, which he witnessed every day, all around him in exile. As Dan Parker has written here on MT numerous times, economic development itself may be one of the best preventives we know. But it may not always be enough. It doesn't much matter which link in the chain of infection is broken; once repaired, we may have to figure out new ways to break the chain again.

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